Advanced integration and packaging will drive the scaling of computing systems in the next decade. Diversity in performance, cost and scale of the emerging systems implies that system technology co-optimization (STCO) would be essential to develop these integration technologies for future systems. Such STCO would need to comprehend not only integration technology, circuits, architectures and software but also their interactions with the power delivery, cooling and system costs. In this Review, we present a perspective on what would be needed from these STCO approaches with exemplar case studies covering the current state of the art and the future outlook.